DESCRIPTION: With the increased use of cochlear implants for the clinical treatment of profound sensorineural hearing loss, it has become critical to learn as much as possible about the nerve being stimulated - the primary auditory nerve. Our goal is to determine how unique combinations of endogenous ion currents affect signal processing in these neurons. Our previous studies have shown that spiral ganglion neurons can be separated into two electrophysiological classes based upon their firing patterns in response to prolonged depolarizing stimuli. One class of neurons display rapid adaptation, a firing pattern that is optimal for signaling stimulus transitions. The other class of cells exhibits slow adaptation, a pattern consistent with encoding stimulus magnitude and duration. Furthermore, spiral ganglion neurons within each of these classes possess multiple kinds of voltage-dependent ion currents that are capable of dynamically altering the membrane potential and responding to extra-synaptic modulation. The presence of intrinsic membrane currents that could alter the threshold, duration, and timing of action potentials that propagate along the length of the neuron implies that these cells have specialized electrophysiological features which may modify and augment synaptically-generated signals as they travel into the central nervous system. Elucidating the types and properties of their membrane currents is, therefore, critical to understanding the functional role of primary auditory neurons. To address this issue, patch clamp recordings will be made from neurons in vitro to examine the elementary properties of their voltage-dependent ion currents. Some experiments will utilize a unique preparation in which recordings can be made from spiral ganglion neurons still attached to their peripheral receptor hair cells in vitro. For detailed analysis of ion channel kinetics and pharmacology, cultured neurons will be studied independent of synaptic influences. Finally, when electrical considerations are paramount, acutely dissociated neurons will be used. These approaches are amenable to characterizations of type II spiral ganglion neuron firing properties, novel heterogeneous hyperpolarization-activated currents, and K+ currents that determine the firing capabilities between and within each neuronal class. Furthermore, the functional significance of these findings will be tested with regard to type I/type II subcategories, frequency coding, spontaneous rates, and threshold levels. This information will yield new insights into the fundamental mechanisms that regulate cell signaling in the peripheral auditory system.